Evidence that Fgf10 offers therapeutic opportunities after hyperoxic lung injury in mice

1) 10 weeks old Fgf10 mice (50% Fgf10 expression compared to WT) in normoxic condition: Lung function and morphometric analysis. 10 weeks old Fgf10 mice (50% Fgf10 expression compared to WT) in normoxic condition: Lung function and morphometric analysis. 2) BPD model: BPD model: a) Fgf10 and Fgf10 mice were exposed to 85% O 2 from P0-P8. Morphometric analysis and α-Actin/vWF staining were performed at P3. Fgf10 and Fgf10 mice were exposed to 85% O 2 from P0-P8. Morphometric analysis and α-Actin/vWF staining were performed at P3. b) Rosa26;tet(O)Fgf10 (gain-of-function) mice were exposed to 85% O 2 from P0-P8. From P9-P45 the pups were exposed to normoxia and fed either with normal food (control) or doxycycline food (experimental) to activate the transgene Fgf10. Morphometric analysis was carried out at P45. Rosa26;tet(O)Fgf10 (gain-of-function) mice were exposed to 85% O 2 from P0-P8. From P9-P45 the pups were exposed to normoxia and fed either with normal food (control) or doxycycline food (experimental) to activate the transgene Fgf10. Morphometric analysis was carried out at P45. 3) Tolerance study: Rosa26;tet(O)Fgf10 and WT mice (both 10 weeks old) were exposed to doxycycline for 2 weeks. Then survival rate, histology, Ki67 and TUNEL staining were performed. Tolerance study: Rosa26;tet(O)Fgf10 and WT mice (both 10 weeks old) were exposed to doxycycline for 2 weeks. Then survival rate, histology, Ki67 and TUNEL staining were performed. 1) Fgf10 mice under normoxic condition have worse lung function and lung structure compared to WT mice. Fgf10 mice under normoxic condition have worse lung function and lung structure compared to WT mice. 2) All Fgf10 mice die from hyperoxic injury due to increased lung injury and vascular malformation. All Fgf10 mice die from hyperoxic injury due to increased lung injury and vascular malformation. 3) Overexpression of Fgf10 after hyperoxic injury leads to improvement of lung structure compared to control group without overexpression. Overexpression of Fgf10 after hyperoxic injury leads to improvement of lung structure compared to control group without overexpression. 4) Fgf10 overexpression after hyperoxic injury does not increase mortality and side effects (weight loss, mucosal proliferation due to hypercellularity with no impact on apoptosis) are reversible. Fgf10 overexpression after hyperoxic injury does not increase mortality and side effects (weight loss, mucosal proliferation due to hypercellularity with no impact on apoptosis) are reversible. Fgf10 attenuates hyperoxic lung injury, is well tolerated and should be further studied as a potential therapeutic for BPD.